@article{2802,
  keywords = {Animals, Mice, Humans, Mutation, Methylation, Polycomb Repressive Complex 1, Child, Preschool, Bone Neoplasms, Gene Expression Regulation, Neoplastic, Histones, Methyltransferases, Nucleosomes, Carcinogenesis, Chondroblastoma, Lysine, Methionine, Mutation, Missense, Neoplastic Stem Cells, Sarcoma, Mesenchymal Stem Cells},
  author = {Chao Lu and Siddhant Jain and Dominik Hoelper and Denise Bechet and Rosalynn Molden and Leili Ran and Devan Murphy and Sriram Venneti and Meera Hameed and Bruce Pawel and Jay Wunder and Brendan Dickson and Stefan Lundgren and Krupa Jani and Nicolas De Jay and Simon Papillon-Cavanagh and Irene Andrulis and Sarah Sawyer and David Grynspan and Robert Turcotte and Javad Nadaf and Somayyeh Fahiminiyah and Tom Muir and Jacek Majewski and Craig Thompson and Ping Chi and Benjamin Garcia and C David Allis and Nada Jabado and Peter Lewis},
  title = {Histone H3K36 mutations promote sarcomagenesis through altered histone methylation landscape.},
  abstract = { <p>Several types of pediatric cancers reportedly contain high-frequency missense mutations in histone H3, yet the underlying oncogenic mechanism remains poorly characterized. Here we report that the H3 lysine 36-to-methionine (H3K36M) mutation impairs the differentiation of mesenchymal progenitor cells and generates undifferentiated sarcoma in vivo. H3K36M mutant nucleosomes inhibit the enzymatic activities of several H3K36 methyltransferases. Depleting H3K36 methyltransferases, or expressing an H3K36I mutant that similarly inhibits H3K36 methylation, is sufficient to phenocopy the H3K36M mutation. After the loss of H3K36 methylation, a genome-wide gain in H3K27 methylation leads to a redistribution of polycomb repressive complex 1 and de-repression of its target genes known to block mesenchymal differentiation. Our findings are mirrored in human undifferentiated sarcomas in which novel K36M/I mutations in H3.1 are identified.</p> },
  year = {2016},
  journal = {Science},
  volume = {352},
  pages = {844-9},
  month = {2016 May 13},
  issn = {1095-9203},
  doi = {10.1126/science.aac7272},
  language = {eng},
}